Early High-frequency Oscillations Research Articles

Role of High Frequency Oscillations of Somatosensory Evoked Potentials in Deciphering Pathophysiology of Migraine.

Background Habituation deficit is considered as a neurophysiological abnormality among migraineurs in the interictal period. For clear comprehension and clarity about the mechanism underlying habituation in migraine, a sophisticated method, i.e., high frequency oscillations (HFOs) evoked potentials, have been utilized. However, studies pertaining to this in the Indian context are rare. Objective The aim of the study is to determine the utility of HFO of somatosensory evoked potential (SSEP) in deciphering the pathophysiology of migraine. Materials and Methods Sixty subjects including 30 migraineurs in the interictal period and 30 healthy controls were considered for the study. Median nerve SSEP was recorded in patients and controls by standard protocols. HFO was extracted offline using the Digital zero-phase shift band-pass filtering at 450 and 750 Hz. The early and late HFOs were determined with respect to the N20 peak and were compared between the groups. Results Of total 30 migraineurs, 18 had hemicranial headache and 12 had holocranial headache. N20 latency, P25 latency, N20 onset to peak amplitude, and N20 onset to P25 amplitude were comparable in migraineurs and controls. The intraburst frequency of early HFOs in migraineurs was significantly higher ( p = 0.04), whereas the peak-to-peak amplitude was significantly lower ( p = 0.001). Conclusion Early HFOs on SSEP represent the thalamocortical excitatory drive in migraineurs. Overall, the study reports that reduced amplitude of early HFOs in the interictal period suggest reduced thalamocortical drive in migraineurs.

Short-latency afferent inhibition and somato-sensory evoked potentials during the migraine cycle: surrogate markers of a cycling cholinergic thalamo-cortical drive?

BackgroundShort-latency afferent inhibition (SAI) consists of motor cortex inhibition induced by sensory afferents and depends on the excitatory effect of cholinergic thalamocortical projections on inhibitory GABAergic cortical networks. Given the electrophysiological evidence for thalamo-cortical dysrhythmia in migraine, we studied SAI in migraineurs during and between attacks and searched for correlations with somatosensory habituation, thalamocortical activation, and clinical features.MethodsSAI was obtained by conditioning the transcranial magnetic stimulation-induced motor evoked potential (MEP) with an electric stimulus on the median nerve at the wrist with random stimulus intervals corresponding to the latency of individual somatosensory evoked potentials (SSEP) N20 plus 2, 4, 6, or 8 ms. We recruited 30 migraine without aura patients, 16 between (MO), 14 during an attack (MI), and 16 healthy volunteers (HV). We calculated the slope of the linear regression between the unconditioned MEP amplitude and the 4-conditioned MEPs as a measure of SAI. We also measured SSEP amplitude habituation, and high-frequency oscillations (HFO) as an index of thalamo-cortical activation.ResultsCompared to HV, SAI, SSEP habituation and early SSEP HFOs were significantly reduced in MO patients between attacks, but enhanced during an attack. There was a positive correlation between degree of SAI and amplitude of early HFOs in HV, but not in MO or MI.ConclusionsThe migraine cycle-dependent variations of SAI and SSEP HFOs are further evidence that facilitatory thalamocortical activation (of GABAergic networks in the motor cortex for SAI), likely to be cholinergic, is reduced in migraine between attacks, but increased ictally.

Research Article -Somatosensory Evoked High Frequency Oscillations in a Homogeneous Population of Drug Naive Migraineurs

Introduction: High band pass filtering of evoked potentials have produced the results of decreased early High frequency oscillations (HFOs) in previous studies of migraine patients. However, in most of these studies, the study population has been heterogeneous. The only study till date which used homogenous drug naive group of patients has actually produced contradictory results to the previous studies showing. Aim: We aimed to clarify the status of HFO amplitudes and latencies in drug-naive newly diagnosed patients. Methods: In the present study, we evaluated the 20 newly diagnosed and drug naive migraine patients using electrophysiological assessments using Somatosensory evoked potentials (SSEPs) and compared their SSEP parameters with those of the healthy age and gender matched normal controls. Median nerve SSEP was obtained by standard protocols. High frequency oscillations were extracted from the broad-band evoked potentials by digitally filtering using high pass filtering at 450Hz-1KHz. Early HFOs were identified when occurred before the N20 peak. Results: No differences were observed in the broad-band SSEPs i.e., N20 amplitudes and latencies. The maximal peak to peak amplitudes in the drug naïve migraineurs in between the attacks for the early HFOs (occurring before the N20 peak) were significantly smaller than the normal controls (p=0.046). The number of negative peaks were also fewer in the migraineurs in a statistically nonsignificant way. Discussion: This is the first HFO study on a homogenous population of migraineurs which shows decreased early HFOs, thus implicating weaker thalamocortical activity and contradicting the results by Lai et al1.

13. Somatosensory high-frequency oscillations in chronic migraine

When still episodic, migraine between attacks is characterized by altered thalamo-cortical connections. Less is known about how chronic migraine changes the activity of these connections. Fifteen episodic migraineurs (MO) between attacks and 19 chronic migraine (CM) patients underwent right median-nerve somatosensory evoked potentials (500 sweeps, 4.4 Hz). Patients were compared to a group of 20 healthy volunteers (HV). Digital filter (band-pass 450–750 Hz) was employed to extract high-frequency oscillations (HFOs) superimposed on the conventional broad-band N20 SSEPs. Two phases of the HFOs were identified: an early, reflecting the thalamo-cortical fibers activity, and a later, probably generated by cortical pyramidal cells. In CM the reduced early HFOs amplitude found in MO between attacks disappeared, showing a pattern similar to HVs. This early HFOs normalization was accompanied by a significant shortened latency of the negative oscillatory maximum. The amplitude of the late HFOs was significantly greater in CM than in HV. Our data document that the transformation from episodic to chronic migraine is accompanied by changes in thalamo-cortical connectivity. Whether this electro-functional behavior is primary or secondary to daily headache, reflecting thus an electrophysiological fingerprint of the somatosensory system central sensitization process remains to be determined.

Abnormal sensorimotor plasticity in migraine without aura patients

The period between migraine attacks is characterized by paradoxical responses to repetitive sensory and transcranial magnetic stimulation (TMS). Abnormal long-term cortical functional plasticity may play a role and can be assessed experimentally by paired associative stimulation (PAS), in which somatosensory peripheral nerve stimuli are followed by TMS of the motor cortex. Changes in motor-evoked potential (MEP) amplitudes were recorded in 16 migraine without aura patients (MO) and 15 healthy volunteers (HV) before and after PAS, which consisted of 90 peripheral electrical right ulnar nerve stimulations and subsequent TMS pulses over the first dorsal interosseous (FDI) muscle activation site with a delay of 10ms (excitability depressing) or 25ms (excitability enhancing). As a control experiment of the 31 subjects studied, 8 (4 MO and 4 HV) also underwent PAS10 earlier, the recording of somatosensory high-frequency oscillations (HFOs) reflecting thalamocortical activation (early HFOs). Although PAS10 reduced MEP amplitudes in HV (−17.7%), it significantly increased amplitudes in MO (+35.9%). Although in HV MEP amplitudes were significantly potentiated (+55.1) after PAS25, only a slight, nonsignificant increase was observed in MO (+18.8%). In the control experiment, performed on 8 subjects pooled together, Pearson’s correlation showed an inverse relationship between the percentage of MEP amplitude changes after PAS10 and early HFO amplitudes (r=−0.81; P=.01). Because we observed that the more deficient the long-term PAS-induced change, the more the thalamocortical activation decreased, we hypothesize that the abnormalities in long-term cortical plasticity observed in the interictal period between migraine episodes could be due to altered thalamic control.

Subcortical Hyperexcitability in Migraineurs: A High-Frequency Oscillation Study

An abnormal central nervous system excitability level was found in patients with migraine. Whether it is hyper- or hypo-excitable is still debated. This study aimed to compare the somatosensory high-frequency oscillations (HFOs), which reflected subcortical excitability (early phase) and intracortical inhibition (late phase), between patients with migraine and control subjects. HFOs were recorded from C3'-Fz, using a 500-1000 Hz frequency filter after stimulation at right median nerves at the wrists, and divided into early and late phases based on the N20 peak. Fifty-nine untreated patients (n=24 during ictal period; n=35, interictal) and 22 controls finished the study. In early HFOs, patients both during ictal and interictal periods had higher maximal amplitudes (p=0.039) and area-under-curve (p=0.029) than those of the controls. Regarding the late HFOs, there were no significant differences among these groups. Our study suggests a hyper-excitable state in the subcortical regions in patients with migraine both during interictal and ictal periods.

Somatosensory evoked potentials and high frequency oscillations are differently modulated by theta burst stimulation over primary somatosensory cortex in humans

Objective The effects of theta burst stimulation (TBS) have been extensively investigated in primary motor cortex, where it leads to long-lasting LTP/LTD-like effects on synaptic plasticity. This study aimed to extend these observations to sensory cortex. Methods Fourteen healthy subjects participated in the study. Conditioning 600-pulse intermittent TBS (iTBS) and continuous TBS (cTBS) were delivered to left somatosensory cortex (S1) with an intensity of 80% active motor threshold. Somatosensory evoked potentials (SEPs) were evoked by median nerve electrical stimulation at right wrist. High frequency oscillations (HFOs) were obtained by digital filtering of original SEPs and divided into early and late subcomponents, relative to N20 peak latency. Results Repeated-measures ANOVA showed that iTBS facilitated N20 onset–N20 peak at 15 min and N20 peak–P25 at 15 and 30 min after conditioning, whereas cTBS did not. iTBS left the early and late HFOs unchanged. Conversely, cTBS facilitated the early HFOs, whereas it inhibited the late HFOs at 15 min after conditioning. Conclusions S1-iTBS facilitated SEPs without changes in HFOs whereas cTBS modulated early and late HFOs without changes in SEPs. Significance S1-TBS produces lasting changes in the excitability of intracortical circuits generating SEPs and HFOs differentially through mechanisms of LTP/LTD-like synaptic plasticity.

Very High-Frequency Oscillations (Over 1000 Hz) of Somatosensory-Evoked Potentials Directly Recorded From the Human Brain

The aims of this study were to record high-frequency oscillations (HFOs) associated with somatosensory-evoked potentials from subdural electrodes and to investigate their generators and clinical significance. Six patients who underwent long-term subdural electrode monitoring were studied. Somatosensory-evoked potentials were recorded directly from the subdural electrode after stimulation of the median nerve. Bandpass filter was 10 to 10,000 Hz for conventional somatosensory-evoked potential and 500 to 10,000 Hz for HFO. Three types of HFO were recorded. The first component was early HFO (407-926 Hz), which occurred before N20 peak. The second component was late HFO (408-909 Hz), which occurred after N20 peak. In addition, a novel component was recorded with a range from 1,235 to 2,632 Hz, and this component was termed very HFO. Early and late HFOs were recorded from relatively wide areas centering around the primary motor and primary sensory areas, whereas very HFO was localized around the primary sensory areas. In this study, at least three components of HFO could be identified. Only very HFO was localized around primary sensory areas, suggesting a possibility that very HFO may provide an effective method of identifying the central sulcus.

Somatosensory evoked high-frequency oscillations reflecting thalamo-cortical activity are decreased in migraine patients between attacks

A deficit of habituation in cortical information processing, including somatosensory evoked potentials (SSEPs), is the most consistent neurophysiological abnormality in migraine patients between attacks. To explore further the mechanisms underlying this interictal neural dysfunction, we have studied the high-frequency oscillations (HFOs) embedded in SSEPs because they are thought to reflect spike activity in thalamo-cortical cholinergic fibres (early HFOs) and in cortical inhibitory GABAergic interneurons (late HFOs). Untreated migraine patients with (MA) and without (MO) aura were recorded during (n = 13: nine MO, four MA) and between attacks (n = 29: 14 MO, 15 MA) and compared with healthy volunteers. SSEPs were filtered off-line (digital band-pass between 450 and 750 Hz) to extract the two HFO bursts from the broad-band contralateral N20 somatosensory cortical response obtained by median nerve stimulation. In both migraine groups, amplitudes and latencies of conventional broad-band SSEPs recorded interictally from cervical and parietal active electrodes were not significantly different from those found in healthy volunteers. In contrast, maximum peak-to-peak amplitude and area under the rectified curve of the early HFO burst were significantly smaller in both MA and MO patients than in healthy volunteers. There was no significant difference in the later HFO burst between migraineurs and healthy volunteers. During attacks, all electrophysiological measurements in migraineurs were similar to those found in healthy volunteers. Thalamo-cortical activation, as reflected by the early SSEP HFO burst, may thus be reduced in migraine interictally, but normalizes during an attack, whereas intracortical inhibition, as indexed by the late HFO burst, is normal at any time. This supports the hypothesis that the habituation deficit in migraineurs is due to a reduced pre-activation level of sensory cortices and not to increased cortical excitability or reduced intracortical inhibition.

Functional Dissociation of a Subcortical and a Cortical Component of High-Frequency Oscillations in Human SEPs by Motor Interference

To identify the possibly divergent impact on early and late high-frequency oscillations (HFOs) in human somatosensory evoked potentials (SEPs), we have studied motor interference effects on the HFOs, and the relevance of such effects for the controversy concerning their origins. While the late HFO is thought to be generated in the somatosensory cortex, there is an ongoing discussion whether the early burst is of cortical or subcortical origin. Movements of the index finger were performed in parallel with median nerve SEP recordings. The intracortically generated N20-SEP and the late HFO were attenuated by the motor task, while the brainstem low-frequency P14-SEP and the early HFO remained unaffected. These differing effects are consistent with a generation of the early HFOs by cortical presynaptic activity in terminals of the thalamocortical projection, and confirm a postsynaptic intracortical origin of the late burst subcomponent.

High-Frequency Somatosensory Thalamocortical Oscillations and Psychopathology in Schizophrenia

Human cortical somatosensory evoked potentials (SEPs), which are presumably generated in afferent thalamocortical and early cortical fibers, reveal a burst of superimposed early (N20) high-frequency oscillations (HFOs), around 600 Hz. There is increasing evidence of an imbalance of thalamocortical systems in schizophrenic patients. In order to assess correlations between somatosensory evoked oscillations and symptoms of schizophrenia, we investigated median nerve SEPs in 20 inpatients and their age-matched and gender-matched healthy controls using a multichannel EEG. Dipole source analysis and wavelet transformation were performed before and after application of a 450-Hz high-pass filter. In schizophrenics, the maximum HFOs occurred with a significantly prolonged latency. There was also a higher amplitude (energy) in the low-frequency range of the N20 component compared with the controls. Importantly, amplitudes (energy) of HFOs were inversely correlated with symptoms of formal thought disorder and delusions. Alterations of the thalamocortical somatosensory signal processing in schizophrenia with absence of an early HFO – assumed to be of inhibitory nature – could indicate a dysfunctional thalamic inhibition with increased amplitudes of N20, paralleled by enhanced positive schizophrenic symptoms.

Functional dissociation of a subcortical and cortical component of high-frequency oscillations in human somatosensory evoked potentials by motor interference

To identify the possibly divergent impact on early and late high-frequency oscillations (HFOs) in human somatosensory evoked potentials (SEPs), we have studied motor interference effects on the HFOs, and the relevance of such effects for the controversy concerning their origins. While the late HFO is thought to be generated in the somatosensory cortex, there is an ongoing discussion whether the early burst is of cortical or subcortical origin. Movements of the index finger were performed in parallel with median nerve SEP recordings. The intracortically generated N20-SEP and the late HFO were attenuated by the motor task, while the brainstem low-frequency P14-SEP and the early HFO remained unaffected. These differing effects are consistent with a generation of the early HFOs by cortical presynaptic activity in terminals of the thalamocortical projection, and confirm a postsynaptic intracortical origin of the late burst subcomponent.

Recovery function of and effects of hyperventilation on somatosensory evoked high-frequency oscillation in Parkinson's disease and myoclonus epilepsy

To evaluate recovery function of and effects of hyperventilation (HV) on high-frequency oscillations (HFOs) of median nerve somatosensory evoked potential (SEP), we recorded SEPs in 8 Parkinson's disease (PD) patients with enlarged HFOs, 4 myoclonus epilepsy (ME) patients and 10 healthy volunteers ( N). SEP was recorded from the hand sensory area contralateral to the median nerve stimulated at the wrist. Responses were amplified with filters set at 0.5 and 3000 Hz. HFOs were obtained by digitally filtering raw SEPs from 500 to 1000 Hz. We measured amplitudes of the N20 onset–peak (N20o–p), N20 peak–P25 peak (N20p–P25p), P25 peak–N33 peak (P25p–N33p), the early (1st–2nd) and late (3rd) HFOs. For the recovery function study, paired-pulse stimuli at various interstimulus intervals (20, 50, 100, 150, 200 and 300 ms) were given. To investigate effects of HV, amplitudes of several components of SEPs recorded after HV were compared with those before HV. In PD and ME, the N20o–p recovery curve showed significantly less suppression as compared with those of N. The P25p–N33p recovery curve of ME showed longer suppression than those of N and PD. There were no significant differences in the early or late HFOs recovery curves among three groups. At the dysinhibited state after HV, the late HFO was reduced in association with a significant enlargement of the N20p–P25p amplitude in normal subjects. This suggests that the late HFOs should reflect bursts of inhibitory interneurons. In the ME patients, the early HFOs significantly decreased by HV. The pattern in ME patients may be explained by a kind of compensation for already enhanced SEPs (giant SEP) in the dysinhibited situation. We conclude that (1) Giant HFOs are normally regulated by inhibitory neuronal systems involving in paired stimulation SEP. (2) The late HFOs must reflect bursts of GABAergic inhibitory interneurons.